Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.

Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.

Serum erythropoietin level is increased during stimulation for IVF but not in OHSS.

BACKGROUND: Erythropoietin (Epo) is a potent vascular growth factor that induces angiogenesis and antiapoptotic signalling. We investigated whether the development of numerous follicles and corpora lutea during in vitro fertilization (IVF) cycle affects circulating Epo levels and further, if Epo could be used as a novel marker for ovarian hyperstimulation syndrome (OHSS). METHODS: 24 women were included in the uncomplicated IVF group and 35 women in the OHSS group. Repeated blood samples from both groups were analysed for Epo, progesterone, blood haemoglobin, and creatinine. Follicular fluid from the IVF group was analysed for Epo and progesterone. Repeated measure analysis was performed for the variables and circulating Epo levels were compared between the IVF group and early OHSS. Furthermore, related growth factors, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) were analysed from subgroup of women to test for correlation with Epo. RESULTS: During IVF, circulating Epo increased from natural mid-luteal phase to stimulated mid-luteal phase (median 9.5; 95% CI 7.2-13.4 IU/L and 12.5; 10.3-13.4 IU/L; p = 0.003). In cycles resulting in pregnancy, Epo level decreased 14 days after oocyte pick-up (OPU) and remained low thereafter. In cycles not resulting in pregnancy, Epo level increased again 35 days after OPU. Follicle fluid Epo concentration was 1.5 times higher than the serum concentration (median 15.4; 95% CI 10.4-19.2 IU/L vs. 10.2; 8.8-12.7; p = 0.006). There was no difference in circulating Epo concentration between early OHSS and uncomplicated IVF. Circulating Epo did not correlate with VEGF or HIF-1. CONCLUSIONS: Circulating Epo levels fluctuate during IVF cycle. We hypothesise this may suggest Epo's involvement in ovarian physiology and angiogenesis. However, Epo was not a clinical marker for OHSS.

Intrapartum cardiotocography with simultaneous maternal heart rate registration improves neonatal outcome.

BACKGROUND: Intrapartum cardiotocographic monitoring of fetal heart rate by abdominal external ultrasound transducer without simultaneous maternal heart rate recording has been associated with increased risk of early neonatal death and other asphyxia-related neonatal outcomes. It is unclear, however, whether this increase in risk is independently associated with fetal surveillance method or is attributable to other factors. OBJECTIVE: This study aimed to compare different fetal surveillance methods and their association with adverse short- and long-term fetal and neonatal outcomes in a large retrospective cohort of spontaneous term deliveries. STUDY DESIGN: Fetal heart rate and maternal heart rate patterns were recorded by cardiotocography during labor in spontaneous term singleton cephalic vaginal deliveries in the Hospital District of Helsinki and Uusimaa, Finland between October 1, 2005, and September 30, 2023. According to the method of cardiotocography monitoring at birth, the cohort was divided into the following 3 groups: women with ultrasound transducer, women with both ultrasound transducer and maternal heart rate transducer, and women with internal fetal scalp electrode. Umbilical artery pH and base excess values, low 1- and 5-minute Apgar scores, need for intubation and resuscitation, neonatal intensive care unit admission for asphyxia, neonatal encephalopathy, and early neonatal death were used as outcome variables. RESULTS: Among the 213,798 deliveries that met the inclusion criteria, the monitoring type was external ultrasound transducer in 81,559 (38.1%), both external ultrasound transducer and maternal heart rate recording in 62,268 (29.1%), and fetal scalp electrode in 69,971 (32.7%) cases, respectively. The rates of both neonatal encephalopathy (odds ratio, 1.48; 95% confidence interval, 1.08-2.02) and severe acidemia (umbilical artery pH <7.00 and/or umbilical artery base excess ≤-12.0 mmol/L) (odds ratio, 2.03; 95% confidence interval, 1.65-2.50) were higher in fetuses of women with ultrasound transducer alone compared with those of women with concurrent external fetal and maternal heart rate recording. Monitoring with ultrasound transducer alone was also associated with increased risk of neonatal intubation for resuscitation (odds ratio, 1.22; 95% confidence interval, 1.03-1.44). A greater risk of severe neonatal acidemia was observed both in the ultrasound transducer (odds ratio, 2.78; 95% confidence interval, 2.23-3.48) and concurrent ultrasound transducer and maternal heart rate recording (odds ratio, 1.37; 95% confidence interval, 1.05-1.78) groups compared with those monitored with fetal scalp electrodes. No difference in risk of neonatal encephalopathy was found between newborns monitored with concurrent ultrasound transducer and maternal heart rate recording and those monitored with fetal scalp electrodes. CONCLUSION: The use of external ultrasound transducer monitoring of fetal heart rate without simultaneous maternal heart rate recording is associated with higher rates of neonatal encephalopathy and severe neonatal acidemia. We suggest that either external fetal heart rate monitoring with concurrent maternal heart rate recording or internal fetal scalp electrode be used routinely as a fetal surveillance tool in term deliveries.

Prevalence of fetal anomalies, stillbirth, neonatal morbidity, or mortality in pregnancies complicated by placenta accreta spectrum disorders.

INTRODUCTION: Placenta accreta spectrum disorders (PAS) lead to major complications in pregnancy. While the maternal morbidity associated with PAS is well known, there is less information regarding neonatal morbidity in this setting. The aim of this study is to describe the neonatal outcomes (fetal malformations, neonatal morbidity, twin births, stillbirth, and neonatal death), using an international multicenter database of PAS cases. MATERIAL AND METHODS: This was a prospective, multicenter cohort study based on prospectively collected cases, using the international multicenter database of the International Society for PAS, carried out between January 2020 and June 2022 by 23 centers with experience in PAS care. All PAS cases were included, regardless of whether singleton or multiple pregnancies and were managed in each center according to their own protocols. Data were collected via chart review. Local Ethical Committee approval and Data Use Agreements were obtained according to local policies. RESULTS: There were 315 pregnancies eligible for inclusion, with 12 twin pregnancies, comprising 329 fetuses/newborns; 2 cases were excluded due to inconsistency of data regarding fetal abnormalities. For the calculation of neonatal morbidity and mortality, all elective pregnancy terminations were excluded, hence 311 pregnancies with 323 newborns were analyzed. In our cohort, 3 neonates (0.93%) were stillborn; of the 320 newborns delivered, there were 10 cases (3.13%) of neonatal death. The prevalence of major congenital malformations was 4.64% (15/323 newborns), most commonly, cardiovascular, central nervous system, and gastrointestinal tract malformations. The overall prevalence of major neonatal morbidity in pregnancies complicated by PAS was 47/311 (15.1%). There were no stillbirths, neonatal deaths, or fetal malformations in reported twin gestations. CONCLUSIONS: Although some outcomes may be too rare to detect within our cohort and data should be interpreted with caution, our observational data supports reassuring neonatal outcomes for women with PAS.

Opportunities for, and barriers to, uterus-preserving surgical techniques for placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making. MATERIAL AND METHODS: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered. RESULTS: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%). CONCLUSIONS: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.

Multifetal pregnancy reductions and selective fetocide in a tertiary referral center - a retrospective cohort study.

OBJECTIVES: Multiple pregnancies involve several complications, most often prematurity, but also higher anomaly rates. Reducing fetuses generally improves pregnancy outcomes. We conducted this study to evaluate the obstetrical and neonatal results after multifetal pregnancy reduction (MFPR) in the largest tertiary hospital in Finland. METHODS: This retrospective cohort study included all MFPR managed in Helsinki University Hospital during a 13 year period (2007-2019). Data on pregnancies, parturients and newborns were collected from patient files. The number of fetuses, chorionicities and amnionicities were defined in first-trimester ultrasound screening. RESULTS: There were 54 MFPR cases included in the final analyses. Most often the reduction was from twins to singletons (n=34, 63 %). Majority of these (25/34, 73.5 %) were due to co-twin anomaly. Triplets (n=16, 29.6 %) were reduced to twins (n=7, 13 %) or singletons (n=9, 16.7 %), quadruplets (n=2, 3.7 %) and quintuplets (n=2, 3.7 %) to twins. Most (33/54, 61.1 %) MFPR procedures were done by 15+0 weeks of gestation. There were six miscarriages after MFPR and one early co-twin miscarriage. In the remaining 47 pregnancies that continued as twins (n=7, 14.9 %) or singletons (n=40, 85.1 %) the liveborn rate was 90 % for one fetus and 71.4 % for two fetuses. CONCLUSIONS: Most MFPR cases were pregnancies with an anomalous co-twin. The whole pregnancy loss risk was 11.1 % after MFPR. The majority (70.6 %) of twins were spontaneous, whereas all quadruplets, quintuplets, and 56.3 % of triplets were assisted reproductive technologies (ART) pregnancies. Careful counselling should be an essential part of obstetrical care in multiple pregnancies, which should be referred to fetomaternal units for MFPR option.

The outcome of reduced and non-reduced triplet pregnancies managed in a tertiary hospital during a 15-year-period - a retrospective cohort study.

OBJECTIVES: Triplet pregnancies involve several complications, the most important being prematurity as virtually all triplets are born preterm. We conducted this study to compare the outcomes of reduced vs. non-reduced triplet pregnancies managed in the largest tertiary hospital in Finland. METHODS: This was a retrospective cohort study in the Helsinki University Hospital during 2006-2020. Data on the pregnancies, parturients and newborns were collected from patient records. The fetal number, chorionicity and amnionicity were defined in first-trimester ultrasound screening. The main outcome measures were perinatal and neonatal mortality of non-reduced triplets, compared to twins and singletons selectively reduced of triplet pregnancies. RESULTS: There were 57 initially triplet pregnancies and 35 of these continued as non-reduced triplets and resulted in the delivery of 104 liveborn children. The remaining 22 cases were spontaneously or medically reduced to twins (9) or singletons (13). Most (54.4 %) triplet pregnancies were spontaneous. There were no significant differences in gestational age at delivery between triplets (mean 33+0, median 34+0) and those reduced to twins (mean 32+5, median 36+0). The survival at one week of age was higher for triplets compared to twins (p<0.00001). CONCLUSIONS: Most pregnancies continued as non-reduced triplets, which were born at a similar gestational age but with a significantly higher liveborn rate compared to those reduced to twins. There were no early neonatal deaths among cases reduced to singletons. Prematurity was the greatest concern for multiples in this cohort, whereas the small numbers may explain the lack of difference in gestational age between these groups.

Busy day effect on adverse obstetric outcomes using a nationwide ecosystem approach: Cross-sectional register study of 601 247 hospital deliveries.

OBJECTIVE: To study the busy day effect on selected neonatal adverse outcomes in different sized delivery hospitals and in the entire nationwide obstetric ecosystem. DESIGN: A cross-sectional register study. SETTING: The lowest and highest 10% of the daily delivery volume distribution were defined as quiet and busy days, respectively. The days between (80%) were defined as optimal delivery volume days. The differences in the incidence of selected adverse neonatal outcome measures were analysed between busy versus optimal days and quiet versus optimal days at the hospital category and for the entire obstetric ecosystem level. POPULATION: A total of 601 247 singleton hospital deliveries between 2006 and 2016, occurred in non-tertiary (C1-C4, stratified by size) and tertiary level (C5) delivery hospitals. METHODS: Analyses were performed by the methods of the regression analyses with crude and adjusted odds ratios including 99% CI. MAIN OUTCOME MEASURES: Birth asphyxia. RESULTS: At the ecosystem level, adjusted odds ratio for birth asphyxia was 0.81 (99% CI 0.76-0.87) on busy versus optimal days. Breakdown to hospital categories show that adjusted odds ratios for asphyxia on busy versus optimal days in non-tertiary hospitals (C3, C4) were 0.25 (99% CI 0.16-0.41) and 0.17 (99% CI 0.13-0.22), respectively, and in tertiary hospitals was 1.20 (99% CI 1.10-1.32). CONCLUSIONS: Busy day effect as a stress test caused no extra cases of neonatal adverse outcomes at the ecosystem level. However, in non-tertiary hospitals busy days were associated with a lower and in tertiary hospitals a higher incidence of neonatal adverse outcomes.

International Academy of Perinatal Medicine (IAPM) guidelines for screening, prediction, prevention and management of pre-eclampsia to reduce maternal mortality in developing countries.

Approximately 800 women die from pregnancy or childbirth-related complications around the world every day, 99% of which occur in developing countries. In majority of cases deaths are related to pre-eclampsia and eclampsia. The purpose of new adjusted and simplified IAPM guidelines is specifically lowering maternal mortality by decreasing preventable deaths in developing countries (particularly in remote rural areas) by using rather cheap medicines used to control chronic and gestational hypertension, prevent pre-eclampsia in high-risk pregnancies and treat severe pre-eclampsia and eclampsia. IAPM guidelines should be implemented and evaluated in each developing country respecting specific problems, needs and resources. It is of essential importance to: 1. Identify specific high-risk pregnancies, 2. Commence timely appropriate ASA and calcium supplementation, 3. Organize basic antenatal care and adequate referral of pregnancies with early onset of pre-eclampsia to the appropriate institutions and ensure induction of labour in well-equipped delivery facility for women with near-term and term pre-eclampsia 4. Ensure magnesium sulphate availability to prevent severe pre-eclampsia and eclampsia-related maternal deaths, and 5. Identify specific barriers for implementation of these guidelines and correct them accordingly. Only by systematic implementations of these guidelines, we may have a chance to decrease the mortality of pre-eclampsia an its complications as a killer number one of mothers in developing countries.

Does COVID-19 infection acquired in different pregnancy trimester influence placental pathology?

OBJECTIVES: To determine the morphological characteristics of the placentas from COVID-19 positive mothers in regard to the trimester of COVID-19 infection onset and low weight molecular heparin (LMWH) treatment. METHODS: Placentas were collected in the period April 1st till September 1st 2021 after delivery at Department of Obstetrics and Gynecology University Hospital Split, Croatia, and sent for pathological examination. Medical history and pathology reports were used to collect the data. Pregnant women were divided based on the onset of COVID-19 infection and stratified into low molecular weight heparin (LMWH)+ or LMWH-. Depending on the data distribution, the following test were used: chi-squared test. Student's t-test, Mann-Whitney U test, ANOVA and Kruskal-Wallis test. RESULTS: In 38% of patients the onset of COVID-19 infection was the 1st trimester of pregnancy, in 27% in the 2nd and 35% of women were infected in the 3rd trimester The fetal vascular malperfusion (FVM) occurrence was statistically significantly higher in the LMWH- group and if the onset of infection was in the 2nd trimester, while the perivillous fibrin deposition was most likely to happen if the COVID-19 infection that occured in the 1st trimester of pregnancy. CONCLUSIONS: The onset of COVID-19 infection has the influence on trophoblast damage and subsequent morphological appearance of the placenta. LMWH use in COVID positive pregnant women decreases the rate of the FVM in examined placentas.

Genetic spectrum of prenatally diagnosed skeletal dysplasias in a Finnish patient cohort.

OBJECTIVE: This retrospective cohort study aims to describe the genetic spectrum of fetal skeletal dysplasias detected in a Finnish patient cohort and the diagnostic yield of various analysis methods used. METHOD: A total of 121 pregnancies with prenatally suspected or diagnosed skeletal dysplasia were analyzed between 2013 and 2020. Clinical details and findings from genetic testing were collected. RESULTS: Abnormal ultrasound triggered further testing in most cases. However, there were several cases with increased nuchal translucency and/or abnormal risk ratio in the first trimester combined screening as the initial finding. Further genetic testing was performed in 84/121 (69.4%) cases. A genetic diagnosis was confirmed in 36/84 (42.9%) cases. Half of the identified cases could be attributed to a founder mutation specific to the Finnish Disease Heritage, whereas the other half consisted of a variety of other genetic defects. CONCLUSION: In our patient cohort, the overall genetic spectrum of prenatally diagnosed skeletal dysplasias was wide. However, the impact of Finnish founder mutations was considerable, suggesting that the genetic spectrum of skeletal dysplasias may differ significantly between populations. This should be taken into consideration during the diagnostic process especially as initial ultrasound findings may be unspecific and the interpretation of ultrasound features is usually difficult.

Busy day effect on the use of obstetrical interventions and epidural analgesia during labour: a cross-sectional register study of 601 247 deliveries.

BACKGROUND: Daily delivery volume might affect the quality of obstetric care. We explored the busy day effect on selected obstetrical interventions and epidural analgesia performed during labour in different sized delivery hospitals and on the Finnish obstetric ecosystem. METHODS: We conducted a cross-sectional study on Finnish Medical Birth Register data of singleton pregnancies (N = 601,247) from 26 delivery hospitals from 2006 to 2016. Delivery hospitals were stratified by annual delivery volume: C (category) 1: < 1000, C2: 1000-1999, C3: 2000-2999, C4: ≥3000, and C5: university hospitals. The exposure variables were defined as quiet, optimal, and busy days determined based on daily delivery volume distribution in each hospital category. Quiet and busy days included approximately 10% of the lowest and highest delivery volume days, while the rest were defined as optimal. Outcome measures were unplanned caesarean section (CS), instrumental delivery, induction of labour, and epidural analgesia. We compared the incidence of outcomes in quiet vs. optimal, busy vs. optimal, and busy vs. quiet days using logistic regression. The statistical significance level was set at 99% to reduce the likelihood of significant spurious findings. RESULTS: In the total population, the incidence of instrumental delivery was 8% (99% CI 2-15%) lower on quiet than on optimal days. In smaller hospitals (C1 and C2), unplanned caesarean sections were performed up to one-third less frequently on busy than optimal and quiet days. More (27%, 99% CI 12-44%) instrumental deliveries were performed in higher delivery volume hospitals (C4) on busy than quiet days. In C1-C3, deliveries were induced (12-35%) less often and in C5 (37%, 99% CI 28-45%) more often on busy than optimal delivery days. More (59-61%) epidural analgesia was performed on busy than optimal and quiet days in C4 and 8% less in C2 hospitals. CONCLUSIONS: Pooled analysis showed that busyness had no effect on outcomes at the obstetric ecosystem level, but 10% fewer instrumental deliveries were performed in quiet than on busy days overall. Furthermore, dissecting the data shows that small hospitals perform less, and large non-tertiary hospitals perform more interventions during busy days.

Excellent perinatal outcome of monoamniotic twin pregnancy with timely diagnosis and optimal management - a retrospective cohort study.

OBJECTIVES: Monoamniotic twins represent a high-risk pregnancy requiring intense follow-up, elective birth and careful consideration of the mode and timing of delivery. We conducted this study to evaluate the perinatal and neonatal outcomes of monoamniotic twin pregnancies in the largest tertiary hospital in Finland. METHODS: This was a retrospective cohort study including all monoamniotic twin pregnancies during a 17-year period (2002-2018) managed in Helsinki University Hospital. Data on mothers and children were collected from patient files. Chorionicity and amnionicity were defined in first-trimester ultrasound screening. RESULTS: There were altogether 31 monoamniotic twin pregnancies during the study period, including four cases of conjoined twins which all underwent termination of pregnancy, and three miscarriages. In the remaining 24 pregnancies that continued past 24 weeks of gestation there was 97.9% survival (one intrauterine death). Three pregnancies were complicated with twin-to-twin transfusion syndrome. All children were delivered by cesarean section with a mean gestational age of 32 + 5 weeks (27 + 1-34 + 2 weeks). Respiratory distress syndrome (RDS) was observed in 57% (27/47) of neonates and grade I-II intraventricular haemorrhage (IVH) in 6.3% (3/47) of neonates. There were no neonatal deaths and no maternal complications. CONCLUSIONS: Monoamniotic twinning is a rare form of pregnancy and carries risks for perinatal and neonatal complications. With timely diagnosis, close monitoring in specialized feto-maternal unit and elective delivery at 32-34 weeks the outcome is usually excellent.

Stillbirth aftercare in a tertiary obstetric center - parents' experiences.

OBJECTIVES: This study aimed to assess parents' satisfaction with received care and support when experiencing stillbirth. METHODS: This was a questionnaire survey conducted at Helsinki University Hospital, Helsinki, Finland during 2016-2020. Separate questionnaires were sent to mothers and partners who had experienced an antepartum singleton stillbirth at or after 22 gestational weeks during 2016-2019. The questionnaire covered five major topics: stillbirth diagnosis, delivery, information on postmortem examinations, aftercare at the ward, and follow-up appointment. RESULTS: One hundred nineteen letters were sent and 57 (47.9%) of the mothers and 46 (38.7%) of their partners responded. Both mothers and their partners felt well supported during delivery. They were also satisfied with the time holding their newborn. Partners reported even higher satisfaction in this aspect with a significant within-dyad difference (p=0.049). Parents were generally pleased with the support at the ward. However, both groups were less satisfied with social worker counseling (mothers 53.7%, partners 61.0%). The majority felt that the follow-up visit was helpful. Nonetheless, a remarkable proportion felt that the follow-up visit increased their anxiousness (25.9%, 14.0%, p=0.018). Partners rated their mood higher than mothers (p=0.001). Open feedback revealed that the support received after discharge from hospital was often insufficient. CONCLUSIONS: Our study showed that the parents who experience stillbirth in our institution receive mostly adequate care and support during their hospital stay. However, there is room for further training of healthcare professionals and other professionals contributing in stillbirth aftercare.

Cost of providing cell-free DNA screening for Down syndrome in Finland using different strategies.

OBJECTIVES: A financial analysis is carried out to assess costs and benefits of providing cell-free DNA screening in Finland, using different strategies. METHODS: Three cell-free DNA screening strategies are considered: Primary, all women; Secondary, those with positive Combined test; and Contingent, the 10-30% with the highest Combined test risks. Three costs are estimated: additional cost for 10,000 pregnancies compared with the Combined test; 'marginal' cost of avoiding a Down syndrome birth which occurs in a pregnancy that would have been false-negative using the Combined test; and marginal cost of preventing the iatrogenic loss of a non-Down syndrome birth which occurs in a pregnancy that would have been false-positive. RESULTS: Primary cell-free DNA will require additional funds of €250,000. The marginal cost per Down syndrome birth avoided is considerably less than the lifetime medical and indirect cost; the marginal cost per unaffected iatrogenic fetal loss prevented is higher than one benefit measure but lower than another. If the ultrasound component of the Combined test is retained, as would be in Finland, the additional funds required rise to €992,000. Secondary cell-free DNA is cost-saving as is a Contingent strategy with 10% selected but whilst when 20-30% costs rise they are much less than for the Primary strategy and are cost-beneficial. CONCLUSIONS: When considering the place of cell-free DNA screening it is important to make explicit the additional and marginal costs of different screening strategies and the associated benefits. Under most assumptions the balance is favorable for Contingent screening.

Delivery characteristics in pregnancies with stillbirth: a retrospective case-control study from a tertiary teaching hospital.

OBJECTIVES: We compared delivery characteristics and outcome of women with stillbirth to those with live birth. METHODS: This was a retrospective case-control study from Helsinki University Hospital, Finland. The study population comprised 214 antepartum singleton stillbirths during 2003-2015. Two age-adjusted controls giving live birth in the same year at the same institution were chosen for each case from the Finnish Medical Birth Register. Delivery characteristics and adverse pregnancy outcomes were compared between the cases and controls, adjusted for gestational age. RESULTS: Labor induction was more common (86.0 vs. 22.0%, p<0.001, gestational age adjusted odds ratio [aOR] 35.25, 95% confidence interval [CI] 12.37-100.45) and cesarean sections less frequent (9.3 vs. 28.7%, p<0.001, aOR 0.21, 95% CI 0.10-0.47) among women with stillbirth. Duration of labor was significantly shorter among the cases (first stage 240.0 min [115.0-365.0 min] vs. 412.5 min [251.0-574.0 min], p<0.001; second stage 8.0 min [0.0-16.0 min] vs. 15.0 min [4.0-26.0 min], p<0.001). Placental abruption was more common in pregnancies with stillbirth (15.0 vs. 0.9%, p<0.001, aOR 8.52, 95% CI 2.51-28.94) and blood transfusion was needed more often (10.7 vs. 4.4%, p=0.002, aOR 6.5, 95% CI 2.10-20.13). The rates of serious maternal complications were low. CONCLUSIONS: Most women with stillbirth delivered vaginally without obstetric complications. The duration of labor was shorter in pregnancies with stillbirth but the risk for postpartum interventions and bleeding complications was higher compared to those with live birth.

Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of the late preterm delivery regardless of the membrane status.

OBJECTIVES: To compare the immunohistochemical expression of IL-6 in placental membranes of late preterm delivery in women with histologically proven chorioamnionitis with and without preterm premature rupture of membranes (PPROM). METHODS: Fetal membranes were collected from 60 women who had late preterm delivery with histologic chorioamnionitis with and without PPROM (30 in each group). Immunohistochemistry for IL-6 was performed on formalin fixed and paraffin-embedded sections. The two groups were matched for age, body mass index and parity. SPSS Version 17.0 was used for statistical analysis. RESULTS: There was no difference in immunohistochemical expression of IL-6 in placental membranes of women with histologic chorioamnionitis regardless of the membrane status. CONCLUSIONS: Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of women with late preterm delivery despite the clinical presentation.

Prenatal array comparative genomic hybridization in a well-defined cohort of high-risk pregnancies. A 3-year implementation results in a public tertiary academic referral hospital.

OBJECTIVE: To find out whether the diagnostic yield of prenatal array comparative genomic hybridization (aCGH) can be improved by targeting preselected high-risk pregnancies. METHOD: All the in-house arrays ordered by the Fetomaternal Medical Center from February 2016 until December 2018 were retrospectively analyzed. The indications for array analysis included fetal structural abnormalities, increased nuchal translucency ≥3.5 mm and a chromosomal abnormality in a parent or a sibling. Common aneuploidies were excluded. RESULTS: Diagnostic yield was 15.1% in the entire patient cohort and as high as 20% in fetuses with multiple structural anomalies. The diagnostic yield was lowest in the group with isolated growth retardation. A total of 76 copy number variants (CNVs) were reported from a total of 65 samples, including 16 CNVs associated with a well-described microdeletion/microduplication syndrome, six autosomal trisomies in mosaic form, and three pathogenic single-gene deletions with dominant inheritance and 12 CNVs known to be risk factors for eg developmental delay. CONCLUSION: The diagnostic yield of aCGH was higher than what has previously been reported in less defined patient cohorts. However, the number of CNVs with unclear correlation to the fetal ultrasound findings was still relatively high. The importance of adequate pre- and posttest counseling must therefore be emphasized.

Busy day effect on intrapartum adverse maternal outcomes - a population-based study of 601 247 singleton deliveries.

BACKGROUND: This was a retrospective population-based study, utilizing the data of 601 247 singleton hospital deliveries collected from the Finnish Medical Birth Register (MBR) in 2006-2016. The aim of this study was to analyse the busy day effect on intrapartum adverse maternal outcomes. METHODS: To implement the study design, daily delivery frequencies and ranges (min-max) for each delivery unit (n = 26) were stratified to the daily delivery volume distributions by the delivery unit's annual delivery volume and profile: Category (C)1 < 1000, C2 1000-1999, C3 2000-2999, C4 ≥ 3000 and C5 the profile of university hospitals. To study the busy day effect, the quiet, optimal and busy days were defined by calculating the number of days (%) with the lowest and highest daily delivery frequencies and summed to the nearest 10 % in each hospital category. Optimal days were determined by calculating approximately 80 % of deliveries occurring between the lowest 10 %, and highest 10 % in each hospital category. Crude and adjusted odd ratios (ORs) with 99 % confidence intervals (CIs) were used to analyze the busy day effect on adverse maternal outcomes, blood transfusions, manual removal of the placenta and obstetric anal sphincter injuries, separately in each hospital category. RESULTS: The busy day effect was associated with the 28 % (99 % CI 8-52 %) and 25 % (99 % CI 11-40 %) increased need for blood transfusions in C2 and university hospitals (C5), respectively, whereas 22 % (99 % CI 10-31 %) less blood transfusions were needed at university hospitals during quiet days. In C3 hospitals, 83 % (99 % CI 65-92 %) less blood transfusions were needed during busy days. Obstetric and anal sphincter injury rates declined during quiet days by 22 % (99 % CI 3-38 %) only in university hospitals. CONCLUSIONS: The findings of this study identify no specific pattern to the busy day effect for adverse maternal outcomes defined as manual removal of the placenta or obstetric and anal sphincter injuries. However, both quiet and busy days seem to be associated with increased or decreased need for blood transfusions in different sized delivery units. Findings also suggest that quiet days are associated with a decreased number of obstetric and anal sphincter injuries.

Developing a database for multicenter evaluation of placenta accreta spectrum.

Studies of rare, but complex clinical conditions require multicenter cooperation. The International Society for Placenta accreta spectrum (IS-PAS) have established a secure web-based database to analyze pregnancies complicated by PAS. By repeated in-person meetings of the IS-PAS, a core dataset was established. Then, a custom-made, secure online database, capable of receiving strictly anonymized patient-related textual and imaging data and allowing statistical queries was designed, tested, amended and implemented. Between 2008 and 2019, 14 IS-PAS centers across Europe and one center in the USA contributed data for all their PAS cases, containing pregnancy data for a total of 442 pregnant women. Data were analyzed by a designated data analysis sub-group of the IS-PAS. Center characteristics are presented. Based on experiences with previous versions, our new online database now allows an all-encompassing data collection. It has shown its usefulness in the current analysis project.